TY  - JOUR
A1  - Habisov, Sabrina
A1  - Huber, Jessica
A1  - Ichimura, Yoshinobu
A1  - Akutsu, Masato
A1  - Rogova, Natalia
A1  - Löhr, Frank
A1  - McEwan, David G.
A1  - Johansen, Terje
A1  - Đikić, Ivan
A1  - Dötsch, Volker
A1  - Komatsu, Masaaki
A1  - Rogov, Vladimir V.
A1  - Kirkin, Vladimir
T1  - Structural and functional analysis of a novel interaction motif within UFM1-activating enzyme 5 (UBA5) required for binding to ubiquitin-like proteins and ufmylation
T2  - Journal of biological chemistry
N2  - The covalent conjugation of ubiquitin-fold modifier 1 (UFM1) to proteins generates a signal that regulates transcription, response to cell stress, and differentiation. Ufmylation is initiated by ubiquitin-like modifier activating enzyme 5 (UBA5), which activates and transfers UFM1 to ubiquitin-fold modifier-conjugating enzyme 1 (UFC1). The details of the interaction between UFM1 and UBA5 required for UFM1 activation and its downstream transfer are however unclear. In this study, we described and characterized a combined linear LC3-interacting region/UFM1-interacting motif (LIR/UFIM) within the C terminus of UBA5. This single motif ensures that UBA5 binds both UFM1 and light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAP), two ubiquitin (Ub)-like proteins. We demonstrated that LIR/UFIM is required for the full biological activity of UBA5 and for the effective transfer of UFM1 onto UFC1 and a downstream protein substrate both in vitro and in cells. Taken together, our study provides important structural and functional insights into the interaction between UBA5 and Ub-like modifiers, improving the understanding of the biology of the ufmylation pathway.
KW  - isothermal titration calorimetry (ITC)
KW  - nuclear magnetic resonance (NMR)
KW  - protein motif
KW  - signal transduction
KW  - x-ray crystallography
KW  - LC3/GABARAP
KW  - LIR
KW  - UBA5
KW  - UFIM
KW  - UFM1
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77265
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-772658
SN  - 0021-9258
VL  - 291.2016
IS  - 17
SP  - 9025
EP  - 9041
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -